Development of new-onset psoriasis while on anti-TNFalpha treatment.
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Adalimumab↗
Biomedical subjects
O FitzGerald
Publications and source records attributed to O FitzGerald.
Rheumatologists' judgements about the efficacy of anti-TNF therapy in two neighbouring regions.
OBJECTIVES: The requirement in Northern Ireland to prescribe biological agents according to National Institute for Clinical Excellence/British Society for Rheumatology (NICE/BSR) guidelines and within a fixed budget has created a waiting list for treatment that has no parallel in the Republic of Ireland. The study investigated the bearing this situation may have had on consultants' judgements in the respective areas. METHODS: Seventy-eight case vignettes created from the data on real patients with RA treated with biologicals in the north and south of Ireland were appraised by nine southern and eight northern consultants, who judged the clinical benefit and significance of the patients' condition after a trial of therapy. Quantitative (clinical judgement analysis) and qualitative (focus groups) techniques were used. RESULTS: Northern consultants perceived a slightly greater degree of clinical benefit after a trial of therapy than southern consultants. Judgement models of northern and southern consultants were broadly comparable. The latter tended to be more uniform in their judgements than the southern group. Focus group discussions with consultants largely validated the findings of the quantitative analysis but revealed how clinical judgement analysis might be misled by gaming strategies. CONCLUSIONS: Despite the absence of overt rationing in the south of Ireland, as far as the judgement of therapeutic benefit from biologicals was concerned, the clinical judgement policies of practitioners were very similar to those in the north. The adoption of NICE/BSR guidelines in the north may have improved the uniformity of clinical practice in Northern Ireland.
Antibodies, Monoclonal↗
Synovial tissue inflammation in early and late osteoarthritis.
OBJECTIVE: To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA). METHODS: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-kappaB activation, expression of tumour necrosis factor alpha (TNFalpha) and interleukin 1beta (IL1beta), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E2 (PGE2) RESULTS: Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001). Numbers of cells producing TNFalpha and IL1beta were also significantly greater in early OA (p<0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-kappaB1 (p<0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups. CONCLUSION: Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.
Aged↗
Immunopathology of psoriasis and psoriatic arthritis.
Psoriatic arthritis (PsA) is characterised by several unique clinical features that differentiate it from rheumatoid arthritis (RA). Attempts to identify immunopathological mechanisms, some shared with psoriasis, that underlie these differences from RA have been most challenging. Recent research studies, however, highlight novel findings in PsA at the molecular, cellular, and tissue levels that form the basis for a new understanding of this relatively common form of inflammatory arthritis. In particular, the availability of new, biological antitumour necrosis factor alpha therapies have allowed further insight into the immunopathology of psoriasis and PsA. This brief review focuses on immunohistological studies in psoriatic skin, PsA synovium, and bone to demonstrate how these data advance our knowledge of disease pathogenesis.
Arthritis, Psoriatic↗
Suprascapular nerve block in chronic shoulder pain: are the radiologists better?
BACKGROUND: Suprascapular nerve block is a safe and effective treatment for chronic shoulder pain in arthritis, which can be performed either by direct imaging (CT guided) or in the clinic using anatomical landmarks to determine needle placement. OBJECTIVE: To compare a CT guided versus an anatomical landmark approach in a randomised, single blind trial examining the efficacy of suprascapular nerve block for shoulder pain in patients with degenerative joint/rotator cuff disease. METHODS: 67 patients with chronic shoulder pain from degenerative disease participated in the trial. 77 shoulders were randomised. The group randomised to receive the block through the anatomical landmark approach received a single suprascapular nerve block. Those in the CT guided group received an injection of methylprednisolone acetate and a smaller volume of bupivacaine around the suprascapular nerve. The patients were followed up for 12 weeks by a "blinded" observer and reviewed at weeks 1, 4, and 12 after the injection. RESULTS: Significant improvements were seen in all pain scores and disability in the shoulders receiving both types of nerve block, with no significant differences in the improvement in pain and disability between the two approaches at any time. Improvements in pain and disability scores were clinically and statistically significant. No significant adverse effects occurred in either group. Patient satisfaction scores for pain relief using either approach were high. CONCLUSION: The CT guided control and landmark approaches to performing suprascapular nerve blocks result in similar significant and prolonged pain and disability reductions; both approaches are safe.
Aged↗
Synovial tissue interleukin-18 expression and the response to treatment in patients with inflammatory arthritis.
OBJECTIVE: To measure synovial tissue interleukin-18 (IL-18) expression in patients with inflammatory arthritis, and to identify associations with serum levels, disease activity, and response to treatment. METHODS: Synovial tissue biopsies and serum samples were obtained from patients with early, active, rheumatoid arthritis (RA) (n = 12), undifferentiated seronegative arthritis (SnA) (n = 9), psoriatic arthritis (PsA) (n = 5), and reactive arthritis (ReA) (n = 2) before and one year after introduction of disease modifying antirheumatic drug (DMARD) treatment. Osteoarthritis (OA) tissues were compared. Tissue IL-18 expression was determined after immunohistochemical staining using a semiquantitative scale. Serum IL-18 was measured by enzyme linked immunosorbent assay. RESULTS: Before treatment was started, tissue IL-18 expression was increased in each diagnostic group compared with OA (p<0.05). Tissue IL-18 expression was correlated with serum C reactive protein levels (r = 0.53, p = 0.003) but not with serum IL-18. After DMARD treatment, 12 patients (five RA, four SnA, three PsA) were re-evaluated. Decreases in tissue IL-18 expression were observed in eight, although the trend did not reach significance (p = 0.068). Changes in tissue IL-18 expression were correlated with changes in serum IL-18 (r = 0.62, p = 0.041) and C reactive protein (r = 0.72, p = 0.009). CONCLUSIONS: Synovial tissue IL-18 expression was correlated with disease activity in inflammatory arthritis. After treatment, tissue levels changed in parallel with changes in serum IL-18 and with changes in the acute phase response. These observations support a role for IL-18 in the pathophysiology of inflammatory arthritis.
Acute Disease↗
A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience.
OBJECTIVE: To determine the clinical presentation and clinical and radiological outcome of early psoriatic arthritis (PsA) at 1 and 2 yr. METHODS: Patients with PsA were assessed at the St. Vincent's University Hospital Early Synovitis Clinic. Standardized clinical and laboratory assessment was performed at presentation and 1- and 2-yr follow-up. Radiographs of the hands and feet were evaluated in chronological order by two trained observers using the Sharp method modified to include the distal interphalangeal (DIP) joints. RESULTS: A total of 129 (12.7%) of 1018 patients were diagnosed with PsA [mean age at onset of arthritis was 40.4 yr (range 11-76); mean duration of disease was 9.9 months (range 0.3-48); 52 oligoarticular, 77 polyarticular]. Means and standard deviations of indices of disease activity at presentation were: 10-cm visual analogue scale = 4.8 +/- 2.7, HAQ score = 0.71 +/- 0.64, ACR functional class III/IV = 41 (35%), Ritchie Articular Index = 5.6 +/- 6, swollen joint count = 6.9 +/- 8, erythrocyte sedimentation rate = 24 +/- 26.4 mm/h, C-reactive protein = 27.6 +/- 58.5 mg/l. At presentation, 49 (38%) patients had peripheral enthesopathy, 13 patients (10%) had inflammatory spine pain and 50 (39%) patients had DIP involvement. A total of 119 had psoriasis at the time of presentation [plaque psoriasis in 112 (94%), mean age of psoriasis onset was 29.8 +/- 16.2 yr, nail dystrophy present in 78 patients (67%)]. At 1 yr of follow-up, 119 (92%) patients were reassessed and 70 (59%) were taking a disease-modifying anti-rheumatic drug (DMARD). At 2 yr, 97 (75%) patients were reassessed and 54 (56%) were taking a DMARD. Despite considerable improvement in inflammation and function scores, only 31 (26%) patients were in remission at 1 yr with 20 (21%) in remission at 2 yr. There was a low rate of DMARD-free remission [14 (12%) at 1 yr and 11 (11%) at 2 yr]. Radiographs of hands and feet were obtained for 117 (91%) patients at presentation and 86 (67%) patients at a median follow-up of 24 months (range 11-56); 47% of patients had joint erosions in hands or feet at follow-up with a mean Sharp erosion score of 3 (0) +/- 5.2 (range 0-25) and a mean Sharp narrowing score of 3.2 (0) +/- 7.5 (range 0-48). CONCLUSION: This study confirms that PsA is a chronic, progressive disease in the majority of patients. Despite clinical improvement with current DMARD treatment, PsA results in radiological damage in up to 47% of patients at a median interval of 2 yr.
Adolescent↗
Increased bone resorption and failure to respond to antiresorptive therapy in progressive dystrophic calcification.
The aim of this study was to evaluate strategies to halt the progression of severe dystrophic calcification in a patient with progressive systemic sclerosis (PSS) and to monitor serial changes in biochemical markers of bone resorption and indices of calcium (Ca) metabolism in response to therapy. The relationship of bone turnover to the extent of dystrophic calcification was also investigated in a number of additional patients with varying degrees of calcinosis. Serial markers of bone turnover and indices of Ca metabolism were measured over a 3-year period in one patient with PSS and severe dystrophic calcification. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA). Bone turnover in this patient and two additional patients with PSS or dermatomyositis (DM) and severe dystrophic calcification (Group A, n = 3) was compared with that in patients with connective tissue disease with little or no evidence of dystrophic calcification (Group B, n = 13). Serial data on one patient with severe progressive calcinosis showed increased bone resorption markers, which remained high over a 3-year period despite antiresorptive therapy. BMD was low. Patients with PSS/DM with severe dystrophic calcification had higher bone resorption than those with minimal or no evidence of calcification. Mean serum ionized Ca and urinary Ca excretion were both lower in those with severe calcinosis. Bone resorption was increased in patients with connective tissue disease and severe dystrophic calcification. Several antiresorptive agents were shown to be ineffective in limiting either bone turnover or clinical progression in one patient.
Absorptiometry, Photon↗
A classification study of clinical subsets in an inception cohort of early psoriatic peripheral arthritis--'DIP or not DIP revisited'.
INTRODUCTION: Multiple psoriatic arthritis (PsA) classification criteria exist, but these are based on established PsA when pre-existing joint damage and the effect of medication may confound their validity. This study examined the application of the Veale classification criteria in early PsA to determine the effect of disease progression and treatment on classification and to determine the effect of the number of involved joints and the presence of distal interphalangeal (DIP) joint involvement at initial presentation on clinical and radiological outcome. METHODS: A total of 129 patients presenting with PsA to an Irish early synovitis clinic were assessed at presentation and at 1- and 2-yr follow-up. The Veale criteria were used for PsA classification and the Sharp score of hands and feet was used to quantify radiological outcome. RESULTS: At presentation, 52 (40%) had oligoarticular PsA and 77 (60%) had polyarticular PsA. Patients with polyarticular PsA were administered disease-modifying anti-rheumatic drugs (DMARDs) more frequently than patients with oligoarticular PsA and this resulted in a significant number of polyarticular PsA patients being reclassified as oligoarticular PsA at 1- [27/70 (39%)] and 2-yr [26/53 (49%)] follow-up. Fewer patients initially classified with oligoarticular PsA were reclassified as polyarticular PsA. More patients with oligoarticular PsA at baseline were in DMARD-free remission and there was less radiological damage at 2-yr follow-up. DIP disease was associated with other classic seronegative disease features-enthesopathy and nail dystrophy-but did not influence clinical or radiological outcome and the separation of DIP disease as a distinct subgroup in classification criteria was not supported. Synovitis-acne-pustulosis-hyperostosis (SAPHO) syndrome was not observed as a separate subgroup. CONCLUSION: This study confirms that the application of classification criteria of PsA based on the pattern and number of involved joints may be confounded in established PsA by the effects of DMARDs. The application of classification criteria based on disease pattern prior to treatment may be more useful in studies of pathogenesis and long-term outcome in PsA.
Adolescent↗
Women with established rheumatoid arthritis perceive pain as the predominant impairment of health status.
OBJECTIVE: The aim of this study was to characterize perceptions of health and well-being in women with established rheumatoid arthritis (RA). METHODS: Women aged between 40 and 60 yr with RA for more than 3 yr, and who were receiving stable doses of anti-rheumatic drug therapy, were selected for study. The Arthritis Impact Measurement Scales 2 (AIMS2) was employed to quantify current health status impairments, the impairments that were attributed to RA, perceptions of current health status compared with other women of the same age, and perceptions of future health status. RESULTS: Fifty-eight patients were studied. The full range of 12 AIMS2 dimensions was used when quantifying impairments in health status. The dominant impairment was pain. Moreover, 88% of patients attributed current pain to RA. Fifty-two per cent perceived their health status to be fair, poor or very poor compared with other women of the same age. Twenty-five per cent expected poor future health status, compared with 10% who perceived poor current health status. Only one patient (2%) expected excellent future health status. CONCLUSION: In this study, a large majority of women perceived impairments of health status that they attributed to RA. Pain was perceived as the predominant impairment. Deterioration in health status was anticipated by many. The inclusion of patient perceptions of health status and disease impact as outcome measures in both cross-sectional and longitudinal clinical research protocols merits further study.
Antirheumatic Agents↗
Re: The role of ultrasonography in the diagnosis and management of idiopathic plantar fasciitis.
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Chronic Disease↗
Suprascapular nerve block (using bupivacaine and methylprednisolone acetate) in chronic shoulder pain.
BACKGROUND: Shoulder pain from inflammatory arthritis and/or degenerative disease is a common cause of morbidity in the community. It is difficult to treat and there are limited data on the efficacy of most interventions. Suprascapular nerve block has shown promise in limited trials in reducing shoulder pain. There have been no large randomised placebo controlled trials examining the efficacy of suprascapular nerve block for shoulder pain in arthritis and/or degenerative disease using pain and disability end points. OBJECTIVE: To perform a randomised, double blind, placebo controlled trial of the efficacy of suprascapular nerve block for shoulder pain in rheumatoid arthritis (RA) and/or degenerative disease of the shoulder. METHODS: 83 people with chronic shoulder pain from degenerative disease or RA took part in the trial. If a person had two painful shoulders, these were randomised separately. A total of 108 shoulders were randomised. Patients in the group receiving active treatment had a single suprascapular nerve block following the protocol described by Dangoisse et al, while those in the other group received a placebo injection of normal saline administered subcutaneously. The patients were followed up for 12 weeks by an observer who was unaware of the randomisation and reviewed at weeks 1, 4, and 12 after the injection. Pain, disability, and range of movement data were gathered. RESULTS: Clinically and statistically significant improvements in all pain scores, all disability scores, and some range of movement scores in the shoulders receiving suprascapular nerve block compared with those receiving placebo were seen at weeks 1, 4, and 12. There were no significant adverse effects in either group. CONCLUSION: Suprascapular nerve block is a safe and efficacious treatment for the treatment of shoulder pain in degenerative disease and/or arthritis. It improves pain, disability, and range of movement at the shoulder compared with placebo. It is a useful adjunct treatment for the practising clinician to assist in the management of a difficult and common clinical problem.
Adult↗
Survey of arthroscopy performed by rheumatologists.
OBJECTIVE: To determine the international distribution and practice of arthroscopy performed by rheumatologists and to evaluate proposed guidelines on minimum standards for training in arthroscopy in the context of current clinical practice. METHODS: A questionnaire was sent to all rheumatology centres identified as practising arthroscopy, by (i) searching Medline from 1966 to 1999, (ii) searching the abstract books of the annual general meetings of ACR, BSR and EULAR from 1980 to 1999, and (iii) correspondence with all the centres identified. RESULTS: Thirty-six rheumatology centres were confirmed as performing arthroscopy (24 in Europe, 10 in USA and two in Australia) and 33 (92%) centres completed the questionnaire. Twenty-five (76%) of the 33 centres performing arthroscopy had started to perform it since 1990 and 72 rheumatologists are now trained in arthroscopy. A total of 16532 arthroscopies had been performed (median=220 arthroscopies/centre, range 20-5000); 50.5% of the arthroscopies had a primary clinical indication and 49.5% had a primary research indication. Most centres fulfilled the minimum standards for arthroscopic facilities and the proposed minimum standards in training were acceptable to 76% of respondents. Complication rates were calculated for 15682 arthroscopies where routine follow-up data were available [joint infection, 16 (0.1%); wound infection, 17 (0.1%); haemarthrosis, 141 (0.9%); deep venous thrombosis, 31 (0.2%); neurological damage, 3 (0.02%), thrombophlebitis, 12 (0.08%), other, 8 (0.06%)]. Irrigation volume correlated with wound infection rate (r=0.41, P=0.03) and centres performing cartilage biopsy had a higher rate of haemarthrosis (P=0.007). CONCLUSION: The last decade has seen rapid growth in arthroscopy performed by rheumatologists in an out-patient setting under local and regional anaesthesia. Proposed minimum standards for training in rheumatological arthroscopy reflect current practice accurately and are acceptable to the majority of arthroscopists. Complication rates of rheumatological arthroscopy are similar to those reported in the orthopaedic literature.
Anesthesia, Local↗
Increased serum cartilage oligomeric matrix protein levels and decreased patellar bone mineral density in patients with chondromalacia patellae.
BACKGROUND: Chondromalacia patellae is a potentially disabling disorder characterised by features of patellar cartilage degradation. OBJECTIVE: To evaluate markers of cartilage and bone turnover in patients with chondromalacia patellae. METHODS: 18 patients with chondromalacia patellae were studied. Serum cartilage oligomeric matrix protein (s-COMP) and bone sialoprotein (s-BSP) levels were measured by enzyme linked immunosorbent assay (ELISA) and compared with those of age and sex matched healthy control subjects. Periarticular bone mineral density (BMD) of both knee joints was assessed by dual energy x ray absorptiometry (DXA). RESULTS: s-COMP levels were significantly raised in all patients with chondromalacia patellae compared with healthy control subjects (p=0.0001). s-BSP levels did not differ significantly between the groups (p=0.41). BMD of the patella was significantly reduced in patients with chondromalacia patellae compared with the control subjects (p=0.016). In patients with bilateral chondromalacia patellae, BMD of the patella was lower in the more symptomatic knee joint (p=0.005). Changes in periarticular BMD were localised to the patella and were not present in femoral regions. Neither s-COMP (p=0.18) nor s-BSP (p=0.40) levels correlated with patellar BMD. CONCLUSIONS: Increased s-COMP levels, reflecting cartilage degradation, and reduced BMD localised to the patella may represent clinically useful markers in the diagnosis and monitoring of patients with chondromalacia patellae. Measures of cartilage degradation did not correlate with loss of patellar bone density, suggesting dissociated pathophysiological mechanisms.
Absorptiometry, Photon↗
Peptostreptococcal pericarditis complicating anti-tumour necrosis factor alpha treatment in rheumatoid arthritis.
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Antibodies, Monoclonal↗
Serum interleukin 18 and interleukin 18 binding protein in rheumatoid arthritis.
OBJECTIVE: To measure serum interleukin 18 (IL18) and IL18 binding protein (IL18BP) levels in patients with inflammatory arthropathies, and to identify associations with disease status and the response to treatment. METHODS: Serum samples were obtained before and after methotrexate treatment from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) attending an early arthritis clinic. IL18 and IL18BP were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Sixty patients with RA and 13 with PsA were evaluated. Serum IL18 levels were significantly higher in RA than in PsA (p<0.001). After six months' treatment with methotrexate, IL18 levels were reduced, but the differences were not significant (p=0.052). In cross sectional analyses, no correlations between IL18 levels and measures of disease activity or structural damage in RA were found. In longitudinal analyses, no correlations between IL18 levels and the response to treatment or the degree of progressive joint damage were found. Similarly, IL18BP levels were raised in RA, and were not associated with measures of the clinical status or the response to treatment. CONCLUSION: Raised serum levels of IL18 are consistent with a pathophysiological role in RA. However, in this study measurement of circulating IL18 and IL18BP did not correlate significantly with clinical measures of disease activity or the response to treatment in patients with early RA.
Antirheumatic Agents↗
Involvement of the nuclear orphan receptor NURR1 in the regulation of corticotropin-releasing hormone expression and actions in human inflammatory arthritis.
OBJECTIVE: To examine the regulation and mode of action of peripheral corticotropin-releasing hormone (CRH) in human inflammatory arthritis. METHODS: CRH messenger RNA (mRNA) levels were measured in normal and inflamed synovial tissue and in primary synoviocytes prior to and following cytokine stimulation. Primary synoviocytes were transiently transfected with CRH promoter/reporter constructs, and promoter activity in response to cytokines was assessed. Immunohistochemical staining established CRH receptor expression, and Northern blot analysis confirmed that the nuclear transcription factors NUR77 and NURR1 contributed to synovial CRH receptor-mediated signaling. Primary synoviocytes were treated with pro- and antiinflammatory mediators, and the time course of NURR1 and NUR77 modulation was examined. Nuclear extracts were analyzed by electrophoretic mobility shift assay to determine NURR1 binding to the CRH promoter/enhancer. RESULTS: CRH mRNA was up-regulated in the synovial tissue in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and sarcoid arthritis, but not in normal synovium. Inflammatory cytokines, such as interleukin-1beta and tumor necrosis factor alpha, enhanced the transcriptional activity of the human CRH promoter and increased levels of CRH mRNA in primary synoviocytes. Synovial CRH functioned in a paracrine manner to induce NURR1 and NUR77. NURR1 was abundantly expressed in the inflammatory cells of both RA and PsA synovium. NURR1 and NUR77 were differentially regulated, and NURR1 was the major cytokine-regulated member of the NURR subfamily as well as the mediator of cytokine- and CRH-dependent inflammatory responses in synovium. Furthermore, glucocorticoids dramatically suppressed cytokine- and CRH-induced synovial NURR1 mRNA. CONCLUSION: These data demonstrate the involvement of the transcription factor NURR1 in the regulation of CRH expression and activity in human inflammatory arthritis.
Arthritis, Rheumatoid↗
Synovial tissue protease gene expression and joint erosions in early rheumatoid arthritis.
OBJECTIVE: To relate the expression of proteases in the lining and sublining layers of the synovial membrane to the rate of joint damage during 1 year in patients with early inflammatory arthritis. METHODS: Samples of synovial membrane were obtained by closed-needle biopsy or needle arthroscopy from inflamed knees of 20 patients with early inflammatory polyarthritis (mean disease duration 9.6 months, range 2 weeks to 18 months). Expression of matrix metalloproteinase 1 (MMP-1), cathepsin B (CB), and cathepsin L (CL) was examined using in situ hybridization. Immunohistochemistry was used to identify infiltrating mononuclear cell populations. Radiographs of the hands and feet, performed at presentation and after 1 year, were evaluated for the development of new erosions. RESULTS: Twelve patients had rheumatoid arthritis (RA), 6 had psoriatic arthritis (PsA), 1 had gout, and 1 had an undifferentiated arthritis. Six patients had erosions at presentation. Eleven patients (10 with RA, 1 with PsA) demonstrated at least 1 new erosion after 1 year of followup. MMP-1, CB, and CL messenger RNA (mRNA) were expressed in the synovial membrane of all patients and were present throughout the lining layer, as well as in perivascular cellular infiltrates and endothelial cells in the sublining layer. In the lining layer, the mean percentages of protease mRNA-positive cells per high-power field were higher in those patients who developed new joint erosions than in those without evidence of joint damage. A similar pattern was observed in the sublining layer, where mean numbers of protease mRNA-positive cells were also greater in patients with new joint erosions. There were significant differences between the two groups in MMP-1 mRNA expression in both the lining and sublining layers (P = 0.0007 and P = 0.0027, respectively), as well as in sublining layer CL mRNA expression (P = 0.017), but not in CB mRNA expression. Numbers of lining layer CD68+ cells correlated positively with lining layer MMP-1 mRNA expression (P = 0.043) and with the development of new joint erosions (P = 0.002). CONCLUSION: The detection of MMP-1, CB, and CL in the synovium soon after the onset of symptoms highlights the potential for early joint destruction in patients with RA. High levels of MMP-1 mRNA expression in the lining layer distinguished patients with more rapidly progressive erosive disease. This is the first study to demonstrate features of early synovial pathophysiology that may identify patients at increased risk of developing new joint erosions.
Adult↗